Natural history of multiple sclerosis in a population-based cohort

Background and purpose:  We sought to identify predictive clinical factors of disability during initial course in multiple sclerosis (MS) patients.
Methods:  A total of 2871 MS patients from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort were analyzed. The relationships between baseline demographic, clinical predictors and time to assignment of Expanded Disability Status Scale (EDSS) scores of 3, 4 and 6 were assessed using a Cox regression model.
Results:  Multivariate analysis showed that, for relapsing–remitting patients, a shorter time to assignment of an EDSS score of 4 was associated with an older age of onset of MS and incomplete recovery from the first relapse. Median times were not influenced by gender or the time between the first two relapses. The results also demonstrated that MS progression is independent of the initial clinical data once an EDSS score of 4 is reached rather than a score of 3 because the time from EDSS 3 to assignment of EDSS 4 were correlated with predicting variables. The data were very different for the time between assignment of scores of 4 and 6 because the median times were not influenced by any of the predicting variables.     

Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis

Background:  A short course of intravenous methylprednisolone (IVMP) followed by oral prednisone taper (OPT) is often used for the treatment of relapses in multiple sclerosis (MS). We examined the effect of IVMP plus OPT compared with IVMP only on neurologic disability 1 year after treatment of a relapse in patients with relapsing–remitting multiple sclerosis..
Methods:  Two hundred eighty-five consecutive relapses were analyzed in a retrospective fashion. One hundred fifty-two patients with a total of 171 relapses received IVMP plus an OPT at the time of relapse whilst 112 patients who experienced 114 relapses received IVMP without OPT.
Results:  There was no difference between the two groups in the baseline characteristics as well as the mean or categorical EDSS at baseline, at the time of relapse confirmation, and at months 3, 6 and 12 after relapse confirmation.
Conclusion:  Our observations suggest that OPT following treatment with IVMP for an MS relapse does not lead to improved neurologic outcome after 12 months compared with treatment with IVMP only. Moreover, our findings raise concerns regarding the common practice of using OPT following IVMP. Further studies are indicated to validate our findings and minimize exposure to systemic corticosteroids, well known for systemic toxicity.     

A longitudinal observational study of a cohort of patients with relapsing–remitting multiple sclerosis treated with glatiramer acetate

Immunomodulatory treatments for relapsing–remitting multiple sclerosis (RRMS) are not efficacious or tolerated in all patients. It is important to evaluate alternative classes of treatment in patients failing first-line therapy. The objective of this prospective observational study was to evaluate the efficacy and safety of glatiramer acetate in patients, to whom β -interferons could not be administered. The study included patients with RRMS who were intolerant to or had contraindications to β -interferon. After initiation of glatiramer acetate treatment, follow-up visits were made every 3 months, when data on neurologist-ascertained relapses and disability [Expanded Disability Status Scale (EDSS) score] were collected. Tolerability was evaluated by spontaneous adverse event reporting. Overall, 205 patients were studied and 113 (55.1%) treated for at least 4 years. The proportion of patients presenting over three relapses per year decreased from 51.2% to 8.4% in the 2 years following treatment initiation. Over 5 years of treatment, mean annualized relapse rates and mean EDSS scores remained stable (0.4–0.6 relapses/year and 3.6 ± 1.8–3.3 ± 2.1 respectively). Adverse events were reported by 179 patients, leading to discontinuation of treatment in 10 patients. Patients with RRMS to whom β -interferons cannot be prescribed can benefit from treatment with glatiramer acetate.     

Efficacy of natalizumab in second line therapy of relapsing–remitting multiple sclerosis: results from a multi-center study in German speaking countries

Background:  Natalizumab has been recommended for the treatment of relapsing–remitting multiple sclerosis (RRMS) in patients with insufficient response to interferon-beta/glatiramer acetate (DMT) or aggressive MS. The pivotal trials were not conducted to investigate natalizumab monotherapy in this patient population.
Method:  Retrospective, multicenter study in Germany and Switzerland. Five major MS centers reported all RRMS patients who initiated natalizumab ≥12 months prior to study conduction.
Results:  Ninety-seven RRMS patients were included [69% female, mean age 36.5 years, mean Expanded Disability Status Scale (EDSS) 3.4; 93.8% were pre-treated with DMT], mean treatment duration with natalizumab was 19.3 ± 6.1 months. We found a reduction of the annualized relapse rate from 2.3 to 0.2, 80.4% were relapse free with natalizumab. EDSS improved in 12.4% and 89.7% were progression free (change of >/= 1 EDSS point). Eighty-six per cent of patients with highly active disease (>/= 2 relapses in the year and >/= 1 Gadolinium (Gd)+ lesion at study entry, n  = 20) remained relapse free. The mean number of Gd enhancing lesions was reduced to 0.1 (0.8 at baseline). Discontinuation rate was 8.2% (4.1% for antibody-positivity).
Conclusion:  Natalizumab is effective after insufficient response to other DMT and also in patients with high disease activity.     

The relapse rate of multiple sclerosis changes during pregnancy: a cohort study

Objective – To evaluate the influence of pregnancy and puerperium on the relapse rate of multiple sclerosis (MS).
Methods – We determined retrospectively the yearly mean relapse rate (MRR) during pregnancies occurring in the course of relapsing–remitting MS. We compared the MRR of pregnancy-time with that of non-pregnancy time by paired t -test. Relative risk (RR) of relapses during the pregnancy-time was also compared with that of non-pregnancy time by χ ² analysis and 95% confidence intervals.
Results – From a population of 351 women affected by clinically definite MS, only 70 reported pregnancies during their relapsing–remitting phase of MS for a total of 98 pregnancies. Both MRR ( P  = 0.006) and RR (RR = 0.63, 95% CI = 0.40–0.94) decreased during the three trimesters of pregnancy. RR increased in the first 3 months of puerperium, although this was not statistically significant (RR = 1.36, 95% CI = 0.79–2.20).
Conclusion – Our study confirms that in MS the relapse rate decreases throughout pregnancy and increases during puerperium. This suggests a complex interplay between hormonal and immune factors.     

Relationship between the extent of T2 lesions and the onset of secondary progression in multiple sclerosis

Patients with relapsing–remitting multiple sclerosis (MS) are at risk of converting to a secondary progressive disease course. To assess the relationship between brain magnetic resonance imaging (MRI) findings and onset of secondary progression, we reanalysed the initial brain MRI scans of 90 relapsing–remitting MS patients, who were clinically followed up for at least 10 years (median 14 years) after their scan, for the number and volume of T2 lesions, and for two measures of brain atrophy (bicaudate ratio and third ventricle width). The relationship to development of secondary progression was studied with Cox regression models and Kaplan–Meier survival analyses. At the end of follow-up, 36 patients had become progressive. The presence of more than 10 T2 lesions more than doubled the risk of becoming secondary progressive (hazards ratio 2.36; 95% CI 1.19–4.66). When at least one of the 10 lesions was confluent the risk increased to 3.51 (1.64–7.50). The hazards ratio for an estimated T2 lesion load of more than 800 mm³ was 2.11 (1.07–4.16). Linear brain atrophy measures were not predictive. Our data show a relationship between the extent of brain T2 lesions and the onset of secondary progression in MS.     

Contribution of relapses to disability in multiple sclerosis

The impact of relapses on long-term disability in multiple sclerosis remains unclear; however some evidence suggests that relapses play an important role in determining subsequent prognosis. We report on outcome, prognostic factors for recovery and the contribution of relapses to the accumulation of fixed disability in a large series of patients with documented relapses. Two hundred and seventynine relapses in 182 patients were assessed before, during and after relapse by expanded disability status scale and data analysed to assess degree of recovery. Factors affecting outcome were considered including sex, age and site of relapse. Mean EDSS prior to relapse was 3.73, during relapse 5.18 and post relapse 4.23. Mean interval to post relapse assessment was 127 days post relapse. Mean residual change in EDSS score (pre to post relapse) was 0.50 points. Overall 49.4 % of patients had a residual increase in disability post relapse of at least 0.5 EDSS points and 32.7 % had an increase of at least 1 point. No significant difference was observed in mean residual EDSS for sex, site of relapse or age at relapse or in the proportion of patients with a residual increase in disability of ≥ 1 EDSS point post relapse. 14.4 % of patients had no increase in EDSS score during relapse compared to pre relapse. These results suggest that acute relapses are commonly associated with an objective worsening of disability in the majority of patients with MS and that recovery is incomplete in approximately half and not influenced by gender, age or site of lesion. Therapies which reduce relapse frequency and/or severity might therefore be expected to slow or prevent worsening of disability if initiated prior to the onset of more permanent damage.     

Quality of life in 1000 patients with early relapsing–remitting multiple sclerosis

Background and purpose:  To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing–remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment.
Methods:  Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS).
Results:  A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58–1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51–0.69, P  < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75–0.78) vs. 0.75 (95%CI: 0.74–0.76) at baseline, 95%CI for difference: 0.01–0.03, P  = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons.
Conclusions:  Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems.     

Influence of climatic factors in the incidence of multiple sclerosis relapses in a Portuguese population

Background and purpose:  Environmental factors are thought to be important in multiple sclerosis (MS) pathophysiology. We aimed to evaluate if there was an association between MS relapses and some climatic factors in a Portuguese population.
Methods:  Four year retrospective study analyzing 414 MS relapses in 249 consecutive relapsing–remitting patients. Non-parametric statistics were used to compare the distribution of relapses across months and seasons. Spearman's coefficient was determined to evaluate the correlation between relapses frequency and maximum and minimum atmospheric temperatures, humidity and atmospheric pressure.
Results:  The mean number of relapses was not significantly different between months or seasons. No correlation was found between relapse frequency and any climatic factor.
Conclusion:  Our series is one of the largest addressing the influence of specific climatic factors on MS relapses. The number of clinical MS relapses seems to be unrelated to climatic factors.     

Plasma lipid peroxidation and progression of disability in multiple sclerosis

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels in 23 patients with RRMS with a benign course, 32 with secondary progressive MS, 24 with primary progressive MS and 30 healthy controls. None of the patients had a relapse within the previous 3 months. Progression of disability was evaluated during a follow-up period of 5 years by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP levels elevated in patients with MS compared with controls ( P  < 0.0001), but there was no difference between patients with a benign and progressive disease course. There was no correlation between PFLPP levels and worsening of disability on the EDSS and speed of progression on the MSSS. Our data suggest that there is no relation between the degree of oxidative stress in plasma and progression of disability in MS.     

Cladribine in aggressive forms of multiple sclerosis

Cladribine (2-chlorodeoxyadenosine) is an immunosuppressant drug previously evaluated in multiple sclerosis (MS) with variable results. We report six patients with aggressive relapsing MS who despite a poor response to other therapies had a favourable clinical evolution after cladribine. Four women and two men with a rapid increase in the number and severity of relapses leading to increasing disability [mean Expanded Disability Status Scale (EDSS) 6.42, standard deviation ± 0.58, mean relapse rate per year in the 2 years prior to study entry 2.67 ± 0.75] were retrospectively evaluated. Brain magnetic resonance imaging (MRI) performed in five patients showed active disease with gadolinium-enhancing lesions. Cladribine was given at 0.07 mg/kg/day for five consecutive days once monthly with a total of 2- to 4-monthly courses. After 6 months, mean EDSS decreased to 3.75 ± 1.64 and MRIs showed a decrease or suppression in the number of gadolinium-enhancing lesions. After 1 year from first dose, cladribine dosage was repeated in four patients because of recurrence of relapses with subsequent similar positive clinical results. In the follow-up period (49.33 ± 39.66 months), the mean relapse rate decreased to 0.71 ± 0.55 and no unexpected or serious adverse events were observed.     

Evaluation of response of multiple sclerosis (MS) relapse to oral high-dose methylprednisolone: usefulness of MS functional composite and Expanded Disability Status Scale

To compare the usefulness of multiple sclerosis functional composite (MSFC) to the Expanded Disability Status Scale (EDSS) in assessing functional changes related to relapse. A prospective 12-week follow-up study after relapse was conducted among 14 multiple sclerosis (MS) patients treated with oral high-dose (1 g) methylprednisolone for 3 days. MSFC and the EDSS were assessed on day 0, before treatment and, 1, 4 and 12 weeks afterwards. In relapses, EDSS (2.5 ± 1.2 to 3.8 ± 1.0) and z-score of the MSFC (0.15 ± 0.58 to −0.59 ± 0.70) worsened. After 1 week of treatment, the EDSS improved (3.3 ± 1.2; P  =   0.002) while the MSFC did not change significantly. At week 4, EDSS improvement was maximal (2.8 ± 1.3; P  =   0.001). At week 12, EDSS remained stable whereas z-score continued improving (0.26 ± 0.74). z-9peg-hole-test was the most sensitive subtest. There was correlation between baseline values of both scales (−0.620, P  <   0.05) and between changes due to relapse (−0.535, P  <   0.05). 78.5% of patients had improved at week 4 (35.7% at week 1). There were no serious adverse effects. MSFC and the EDSS were sensitive to changes due to relapses, although the dynamics for restoring baseline function were different. Our data support the usefulness of both scales in clinical trials, providing complementary information about outcome of MS patients with relapses.     

Combination of IFNβ-1a (Avonex®) and mycophenolate mofetil (Cellcept®) in multiple sclerosis

To determine the safety of a combination of mycophenolate mofetil (Cellcept®, MMF) and IFN β -1a (Avonex®) in relapsing-remitting multiple sclerosis (RRMS) and to evaluate the effects of the combination on clinical and magnetic resonance imaging (MRI) measures of disease activity. Secondary objectives were clinical and MRI data. An open-label, single-centre study including 30 RRMS patients was performed. Inclusion criteria were patients expanded disability status scale (EDSS) score <6.0, treated by Avonex® for at least 6 months, with at least two relapses during the previous 2 years and at least one during the previous 6 months. MMF at a progressive dose of 2 g per day orally was added to Avonex® for a duration of 6 months. MRI data were obtained at baseline and at the end of the study. The pre-study annual relapse rate was 2.0 ± 0.7 and the EDSS score at baseline was 2.9 ± 1.3. Eleven patients had gadolinium (Gd)-enhanced lesions at baseline for a total number of 35 lesions. Two patients interrupted the combination, one after the first dose for personal reasons unrelated to the study and the other due to diarrhoea. A few of the patients also reported nausea and abdominal pains. Adverse events included benign infectious diseases, insomnia and dizziness. No significant biological abnormalities were noted. The annualized relapse rate was 0.57 ± 0.3 at the end of the study ( P  < 0.001). The mean EDSS score was 2.6 ± 1.5 and no Gd-enhanced lesions were detected on MRI at the end of the study. MMF and IFN β -1a (Avonex®) combined therapy is safe and very well-tolerated. Clinical and MRI data suggest that this combination may be beneficial.     

Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment

Background and purpose:  Interferon beta and Glatiramer acetate are safe immunomodulatory treatments (IT) for multiple sclerosis (MS), but not always effective. New drugs are available, although they show more side-effects and unknown long-term safety profile. Anti-lipid oligoclonal IgM bands (OCMB) distinguish MS patients with early aggressive course. We prospectively studied if IT are effective in these patients or if they are candidates for more aggressive drugs as first therapeutic option.
Methods:  Seventy-five clinically isolated syndrome patients were studied. OCMB and conversion to MS were assessed. Patients suffering at least two demyelinating events within 3 years were considered eligible to start IT.
Results:  Eighteen patients showed OCMB (M+) and 57 lacked them (M−). All M+ patients and only 25 M− patients were treated. The other 32 M− patients suffered less MS attacks than those required to initiate treatment. IT similarly reduced relapse rate in both treated groups ( P  < 0.0001) and reduced Expanded Disability Status Scale (EDSS) progression in M+ patients, whose EDSS score had significantly increased before treatment. EDSS did not change in M− patients during follow-up, regardless if they were treated or not.
Conclusions:  Oligoclonal IgM bands identify MS patients who are candidates for early immunomodulatory treatment as IT improves their initial aggressive disease course.     

Beta-interferons in multiple sclerosis: A single center experience in India

Background:

Indian-Asian multiple sclerosis behaves somewhat differently from Western disease. It is not known if the response to β-interferon is also different.

Aim:

To demonstrate the decrease in relapses with β-interferon in Indian patients with multiple sclerosis.

Patients and Methods:

Patients with relapsing–remitting or secondary progressive multiple sclerosis with at least two relapses were started on β-interferon.

Results:

Sixteen patients were followed up for a period of 1–3 years. Fifteen had relapsing–remitting multiple sclerosis (MS). The mean number of relapses in these patients before interferons were started was 3.4. The mean yearly relapse rate was 1.3. The mean Kurtzke Expanded Disability Status Scale (EDSS) at the start of β-interferon therapy in relapsing–remitting MS was 1.7. Ten of these patients were on Avonex^® (interferon β1a) and six (including the patient with secondary progressive MS) were on Betaferon^® (interferon β1b). On follow-up, three patients (two on Avonex^® and one on Betaferon^® ) had relapses. The respective β-interferon being received by these patients was continued, with no further relapses. The remaining patients had no relapse or clinical or MRI progression after starting the drug. The side effect profile of the drug in these patients was favorable; although nearly all developed fever on the first day of the injection, only 50% of the patients continued to have fever after 3 months. Two patients developed psychiatric symptoms, requiring discontinuation of the drug.

Conclusion:

Our prospective follow-up study shows that β-interferons are safe and effective in Indian patients with relapsing–remitting or secondary progressive MS.     

The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing–remitting multiple sclerosis patients

The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN β) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN β therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti–inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN β therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN β and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN β alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (r r =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6±1.23 at T0 to 2.2 ± 1.5 at T2, showing only a trend of improvement.No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN β halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).     

A transcranial magnetic stimulation study evaluating methylprednisolone treatment in multiple sclerosis

OBJECTIVE: To investigate the efficacy of two different high doses of intravenous methylprednisolone (IVMP) during Multiple Sclerosis (MS) relapses. BACKGROUND: Transcranial Magnetic Stimulation (TMS) is the most sensitive neurophysiological ascertainment to quantify motor disability, to follow the recovery from an MS relapse, and to detect the response to treatment. DESIGN AND METHOD: Twenty-four clinically definite relapsing - remitting MS patients presenting a relapse were randomly assigned to a treatment for 5 days with IVMP 1 or 2 g/day. The response to treatment of each patient was evaluated through Expanded Disability Status Scale (EDSS), Medical Research Council (MRC) score, and TMS by means of motor evoked potential (MEP) parameters. RESULTS: Motor threshold (MT), central motor conduction time (CMCT) and MRC showed a higher improvement with the highest dose of IVMP. Silent period and EDSS improved with both treatments. CONCLUSION: The dose of 2 g/day of IVMP is more effective in MS relapse.     

Clinical characteristics and long term prognosis in early onset multiple sclerosis

The clinical features, disease course and long term prognosis of early onset multiple sclerosis (EOMS) are variable. A preponderance of female sex, a high incidence of visual and brainstem symptoms at onset and a relapsing–remitting disease course with slower progression rate all have been considered relatively frequent in this subgroup of MS patients. Unfortunately, follow–up in previous studies has usually been limited to less than 10 years, precluding general statements on the long term evolution and prognosis in EOMS. In this retrospective study of EOMS with a substantially longer follow–up of 20.8 years, clinical characteristics, disease course and long term prognosis are described in 49 EOMS patients. In a representative subgroup of 28 patients disability was scored using Kurtzke’s Functional System (FS) and Expanded Disability Status Scale (EDSS). The mean period of follow– up for these patients was 28.7 years. The present study confirms that several specific clinical characteristics can be identified in EOMS patients, such as a mainly relapsing–remitting disease onset and frequent presentation with brainstem– cerebellar dysfunction (28.6 %), pyramidal symptoms (18.4 %) and optic neuritis (14.3%). However, after a long period of follow–up the overall disease course and prognosis do not seem to differ from that in adult onset MS. By consequence a young age at onset in MS cannot be considered a favourable prognostic factor.     

Use of mitoxantrone in early multiple sclerosis with malignant disease course. Observational study in 30 patients with clinical and MRI outcomes after one year

IntroductionIn an observational multicenter study, we analyzed retrospectively 30 patients with malignant form of multiple sclerosis (MS) treated with mitoxantrone the year following the first neurological event.MethodsThe 30 patients were selected according to Weinshenker criteria of malignant MS (either a “catastrophic” relapse or a quickly aggressive form). We compared clinical and MRI findings the year before with the year following mitoxantrone onset treatment: annualized relapse rates (ARR), EDSS score and percentage of patients with gadolinium enhancing lesions on MRI.ResultsA total of 87 relapses were observed in the 5.7 months before and 10 during the year following onset of mitoxantrone treatment. The ARR decreased by 95% (6.0 ± 2 before and 0.3 ± 0.7 after). Twenty-four patients (80%) were relapse-free one year after onset of mitoxantrone treatment. The EDSS score improved in 87% of MS patients and the mean EDSS decreased by 1.9. Ninety-seven percent had at least gadolinium enhancing lesions before the start of mitoxantrone treatment as compared to 17% after.ConclusionIn our experience, mitoxantrone had a rapid and strong impact on the malignant forms of MS with a short disease duration. In this MS subgroup, mitoxantrone should be considered as an early treatment option.     

Long-term clinical experience with weekly interferon beta-1a in relapsing multiple sclerosis

Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFN β -1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFN β -1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 ± 19.3 months. Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with ≤2 relapses in the previous 2 years and with baseline EDSS scores of ≤2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFN β -1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.